Manipulation and use of antigen-specific regulatory T cells
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsNaresha Saligrama, Mark M. Davis, Jing Li
Life of this patent
Estimating the term…
Abstract
Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and/or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin/granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and/or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.
Claims17
A method of expanding in an individual in vivo a population of CD8+ KIR+ human suppressor T cells that selectively suppress activity of CD4+ T cells responsive to a target antigen;
- but are not themselves activated by the target antigen, the method comprising:
- immunizing the individual with a surrogate peptide of any of SEQ ID NO:1-4.
A method of obtaining a population of human regulatory T cells, the method comprising enriching or expanding from an individual for a human cell population of CD8+ KIR+ human regulatory T cells that selectively suppress activity of CD4+ T cells responsive to an initiating antigen;
- the method comprising selecting for cells that express CD8, express one or more of KIR3DL1, KIR2DL3 and KIR2DL2, are restricted to an MHC class I antigen, and express low levels of CD28, to obtain a population of human regulatory T cells.
A method of decreasing a CD4+ T cell response to a target antigen in a subject, the method comprising administering an effective dose of CD8+ KIR+ human regulatory T cells that express CD8, express one or more of KIR3DL1, KIR2DL3 and KIR2DL2, are restricted to an MHC class I antigen, and express low levels of CD28.
Dependencies are inferred from the claim text.